Network pharmacology and experimental evidence: ERK/CREB/BDNF signaling pathway is involved in the antidepressive roles of Kaiyu Zhishen decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: Major Depressive Disorder (MDD) emerges as a complex psychosomatic condition, notable for its considerable suicidality and mortality rates. Increasing evidence suggests the efficacy of Chinese herbal medicine in mitigating depression symptoms and offsetting the adverse effects associated with conventional Western therapeutics. Notably, clinical trials have revealed the adjunctive antidepressant potential of Kaiyu Zhishen Decoction (KZD) alongside Western medication. However, the standalone antidepressant efficacy of KZD and its underlying mechanisms merit in-depth investigation. AIM OF THE STUDY: This research aims to elucidate the impact of KZD on MDD and delineate its mechanistic pathways through integrated network pharmacological assessments and empirical in vitro and in vivo analyses. MATERIALS AND METHODS: To ascertain the optimal antidepressant dosage and mechanism of KZD, a Chronic Unpredictable Mild Stress (CUMS)-induced depression model in mice was established to evaluate depressive behaviors. High-Performance Liquid Chromatography (HPLC) and network pharmacological approaches were employed to predict KZD's antidepressant mechanisms. Subsequently, hippocampal samples were subjected to 4D-DIA proteomic sequencing and validated through Western blot, immunofluorescence, Nissl staining, and pathway antagonist applications. Additionally, cortisol-stimulated PC12 cells were utilized to simulate neuronal damage, analyzing protein and mRNA levels of MAPK-related signals and cell proliferation markers. RESULTS: The integration of network pharmacology and HPLC identified kaempferol and quercetin as KZD's principal active compounds for MDD treatment. Proteomic and network pharmacological KEGG pathway analyses indicated the MAPK signaling pathway as a critical regulatory mechanism for KZD's therapeutic effect on MDD. KZD was observed to mitigate CUMS-induced upregulation of p-ERK/ERK, CREB, and BDNF protein expressions in hippocampal cells by attenuating oxidative stress, thereby ameliorating neuronal damage and exerting antidepressant effects. The administration of PD98059 counteracted KZD's improvements in depression-like behaviors and downregulated p-ERK/ERK and BDNF protein expressions in the hippocampus. CONCLUSIONS: This investigation corroborates KZD's pivotal, dose-dependent role in antidepressant activity. Both in vivo and in vitro experiments demonstrate KZD's capacity to modulate the ERK-CREB-BDNF signaling pathway by diminishing ROS expression induced by oxidative stress, enhancing neuronal repair, and thus, manifesting antidepressant properties. Accordingly, KZD represents a promising herbal candidate for further antidepressant research.

The safety and efficacy of Compound Kushen Injection with chemoradiotherapy for the outcomes of lung and gastrointestinal cancers: A PRIMSA-compliant meta-analysis.

BACKGROUND: Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Radix Sophorae and Smilax glabra Roxb. CKI, as an antitumor preparation, plays a vital role in the clinical treatment of lung and gastrointestinal cancers. METHODS: Electronic databases such as the China National Knowledge Infrastructure, Wanfang data, PubMed, EMBASE, and Web of Science were searched for studies. The included studies were evaluated according to the Cochrane Handbook for Systematic Reviews, and meta-analyses were performed using RevMan 5.3 software. RESULTS: Twenty-four randomized controlled trials were selected for meta-analysis. The outcomes showed that CKI adjuvant therapy significantly improved complete remission (CR) and partial response (PR) compared to patients without CKI treatment in gastrointestinal cancers (CR: odds ratio [OR] = 1.76, 95% confidence interval [CI]: [1.29, 2.41], P = .0004; PR: OR = 1.64, 95% CI: [1.29, 2.07], P =.0001), and lung cancer (CR: OR = 2.18, 95% CI: [1.36, 3.51], P = .001); PR: OR = 1.81, 95% CI: [1.31, 2.50], P = .0003). CKI adjuvant therapy had a statistically significant advantage in optimizing life and health status (quality of life [QOL] for gastrointestinal cancers: MD = 1.76, 95% CI: [6.41, 13.80], P = .001, and Karnofsky performance status [KPS] for gastrointestinal cancers: MD = 4.64, 95% CI: [2.72, 6.57], P = .001; KPS for lung cancer: MD = 6.24, 95% CI [1.78, 10.71], P = .006). CKI reduced the pain in lung cancer patients (MD = -1.76, 95% CI: [-1.94, -1.58], P < .00001), increased immunity level (MD = 2.51, 95% CI: [2.17, 2.85], P < .00001), and alleviated the adverse reactions for lung and gastrointestinal cancers (MD = 0.38, 95% CI: (0.32, 0.46); P < .00001). CONCLUSION: The combination of CKI and chemoradiotherapy for treating lung and gastrointestinal cancer has positive effects on short-term and long-term outcomes and has advantages over chemoradiotherapy alone regarding safety and efficacy.

Kai-xin-san improves cognitive impairment in D-gal and Aß25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood. AIM OF THE STUDY: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota. MATERIALS AND METHODS: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aß25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments. RESULTS: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant. CONCLUSION: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

Efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods.

BACKGROUND: The prevalence of macrolide-resistant Mycoplasma pneumoniae has increased considerably. Treatment in children has become challenging. This study aimed to evaluate the efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods. METHODS: We retrospectively analyzed the data of patients with macrolide-resistant Mycoplasma pneumoniae pneumonia hospitalized between May 2019 to August 2022. According to treatment, patients were divided into three groups: oral doxycycline treatment alone (DOX group), changed from intravenous azithromycin to oral doxycycline (ATD group), and intravenous azithromycin treatment alone (AZI group). ATD group cases were separated into two sub-groups: intravenous azithromycin treatment<3 days (ATD1 group) and ≥ 3 days (ATD2 group). Clinical symptoms were compared in each group and adjusted by Propensity score matching (PSM) analysis. RESULTS: A total of 106 were recruited in this study. 17 (16%) were in DOX group, 58 (55%) in ATD group, and 31(29%) in AZI group. Compared with ATD group and AZI group, the DOX group showed shorter hospitalization duration and fever duration after treatment, while higher rate of chest radiographic improvement. After using PSM analysis, shorter days to hospitalization duration (P = 0.037) and to fever duration after treatment (P = 0.027) in DOX + ATD1 group than in ATD2 group was observed. A higher number of patients in the DOX + ATD1 group achieved defervescence within 72 h (P = 0.031), and fewer children received glucocorticoid adjuvant therapy (P = 0.002). No adverse reactions associated with doxycycline was observed during treatment. CONCLUSIONS: Children receiving early oral doxycycline had a shorter duration of fever and hospitalization in macrolide-resistant Mycoplasma pneumoniae patients.

Amino acid-based metallo-supramolecular nanoassemblies capable of regulating cellular redox homeostasis for tumoricidal chemo-/photo-/catalytic combination therapy.

Nanozymes, as nanomaterials with natural enzyme activities, have been widely applied to deliver various therapeutic agents to synergistically combat the progression of malignant tumors. However, currently common inorganic nanozyme-based drug delivery systems still face challenges such as suboptimal biosafety, inadequate stability, and inferior tumor selectivity. Herein, a super-stable amino acid-based metallo-supramolecular nanoassembly (FPIC NPs) with peroxidase (POD)- and glutathione oxidase (GSHOx)-like activities was fabricated via Pt4+-driven coordination co-assembly of l-cysteine derivatives, the chemotherapeutic drug curcumin (Cur), and the photosensitizer indocyanine green (ICG). The superior POD- and GSHOx-like activities could not only catalyze the decomposition of endogenous hydrogen peroxide into massive hydroxyl radicals, but also deplete the overproduced glutathione (GSH) in cancer cells to weaken intracellular antioxidant defenses. Meanwhile, FPIC NPs would undergo degradation in response to GSH to specifically release Cur, causing efficient mitochondrial damage. In addition, FPIC NPs intrinsically enable fluorescence/photoacoustic imaging to visualize tumor accumulation of encapsulated ICG in real time, thereby determining an appropriate treatment time point for tumoricidal photothermal (PTT)/photodynamic therapy (PDT). In vitro and in vivo findings demonstrated the quadruple orchestration of catalytic therapy, chemotherapeutics, PTT, and PDT offers conspicuous antineoplastic effects with minimal side reactions. This work may provide novel ideas for designing supramolecular nanoassemblies with multiple enzymatic activities and therapeutic functions, allowing for wider applications of nanozymes and nanoassemblies in biomedicine.

The molecular mechanism of action for the potent antitumor component extracted using supercritical fluid extraction from Croton crassifolius root.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Croton crassifolius has been used as a traditional Chinese medicine (TCM), called Radix Croton Crassifolius, and commonly known as "Ji Gu Xiang" in Chinese. Its medicinal value has been recorded in several medical books or handbooks, such as "Sheng Cao Yao Xing Bei Yao", "Ben Cao Qiu Yuan" and "Zhong Hua Ben Cao". It has been traditional employed for treating sore throat, stomach-ache, rheumatism and cancer. AIM OF THE STUDY: At present, there are limited studies on the evaluation of low-polarity extracts of roots in C. crassifolius. Consequently, the aim of this study was to evaluate the antitumor effect of the low-polarity extract of C. crassifolius root. MATERIALS AND METHODS: Extracts were obtained by supercritical fluid extraction. The extracts were tested for antitumor effects in vitro on several cancer cell lines. A CCK-8 kit was used for further analysis of cell viability. A flow cytometer and propidium iodide staining were used to evaluate the cell cycle and apoptosis. Hoechst staining, JC-1 staining and the fluorescence probe DCFH-DA were used to evaluate apoptotic cells. Molecular mechanisms of action were analyzed by quantitative RT‒PCR and Western blotting. Immunohistochemistry was used for the evaluation of xenograft tumors in male BALB/c mice. Finally, molecular docking was employed to predict the bond between the desired bioactive compound and molecular targets. RESULTS: Eleven diterpenoids were isolated from low-polarity C. crassifolius root extracts. Among the compounds, chettaphanin II showed the strongest activity (IC50 = 8.58 µM) against A549 cells. Evaluation of cell viability and the cell cycle showed that Chettaphanin II reduced A549 cell proliferation and induced G2/M-phase arrest. Chttaphanin II significantly induced apoptosis in A549 cells, which was related to the level of apoptosis-related proteins. The growth of tumor tissue was significantly inhibited by chettaphanin II in experiments performed on naked mice. The antitumor mechanism of chettaphanin II is that it can obstruct the mTOR/PI3K/Akt signaling pathway in A549 cells. Molecular docking established that chettaphanin II could bind to the active sites of Bcl-2 and Bax. CONCLUSIONS: Taken together, the natural diterpenoid chettaphanin II was identified as the major antitumor active component, and its potential for developing anticancer therapies was demonstrated for the first time by antiproliferation evaluation in vitro and in vivo.

A Fe(III) intercalated clay nanoplatform for combined chemo/chemodynamic therapy.

A Fe(III) intercalated montmorillonite nanoplatform (Fe-MMT) was engineered for doxorubicin (DOX) loading. The constructed Fe-MMT/DOX nanoplatform could not only improve the production of H2O2 to enhance chemodynamic therapy but interfere with DNA damage repair to amplify the efficacy of DOX, proving an ideal combination of chemotherapy and chemodynamic therapy.

An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2.

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Effectively α-Terpineol Suppresses Glioblastoma Aggressive Behavior and Downregulates KDELC2 Expression.

BACKGROUND: Glioblastoma (GBM) is notorious for the aggressive behaviors and easily results in chemo-resistance. Studies have shown that the use of herbal medicines as treatments for GBM as limited by the blood-brain barrier (BBB) and glioma stem cells. PURPOSE: The aim of this study was to investigate the relationship between GBM suppression and α-terpineol, the monoterpenoid alcohol derived from Eucalyptus glubulus and Pinus merkusii. STUDY DESIGN: Using serial in-vitro and in-vivo studies to confirm the mechanism of α-terpineol on down-regulating GBM development. METHODS: The 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate IC50 of α-terpineol to inhibit GBM cell survival. In order to evaluate the impact of GBM aggressive behaviors by α-terpineol, the analysis of cell migration, invasion and colony formation were implemented. In addition, the ability of tumor spheres and WB of CD44 and OCT3/4 were evaluated under the impression of α-terpineol decreased GBM stemness. The regulation of neoangiogenesis by α-terpineol via the WB of angiogenic factors and human umbilical vein endothelial cells (HUVEC) tube assay. To survey the decided factors of α-terpineol downregulating GBM chemoresistance depended on the impact of O6-methylguanine-DNA methyltransferase (MGMT) expression and autophagy-related factors activation. Additionally, WB and quantitative real-time polymerase chain reaction (qRT/PCR) of KDEL (Lys-Asp-Glu-Leu) containing 2 (KDELC2), endoplasmic reticulum (ER) stress, phosphoinositide 3-kinase (PI3k), mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) cascade signaling factors were examined to explore the mechanism of α-terpineol inhibiting GBM viability. Finally, the orthotopic GBM mouse model was applied to prove the efficacy and toxicity of α-terpineol on regulating GBM survival. RESULTS: α-terpineol significantly suppressed GBM growth, migration, invasion, angiogenesis and temozolomide (TMZ) resistance. Furthermore, α-terpineol specifically targeted KDELC2 to downregulate Notch and PI3k/mTOR/MAPK signaling pathway. Finally, we also demonstrated that α-terpineol could penetrate the BBB to inhibit GBM proliferation, which resulted in reduced cytotoxicity to vital organs. CONCLUSION: Compared to published literatures, we firstly proved α-terpineol possessed the capability to inhibit GBM through various mechanisms and potentially decreased the occurrence of chemoresistance, making it a promising alternative therapeutic option for GBM in the future.

Advances in traditional Chinese herbal medicine and their pharmacodynamic mechanisms in cancer immunoregulation: a narrative review.

Background and Objective: The cancer-immunity cycle (CIC) is defined as a series of progressive events that cause an anticancer immune response leading to the killing of the cancer cell. The concept of CIC has important guiding significance for the clinical and basic tumor immunotherapy research. As one of the methods of traditional Chinese medicine (TCM), Chinese herbal medicine (CHM) has shown unique advantages in multitarget and multipathway immune regulation. However, the tumor immune circulation targeted by CHM is generally unclear at present. To provide reference for future clinical and basic research, we systematically reviewed the existing literature on CHM (including CHM monomers, CHM compounds, and CHM patent medicines) and the mechanisms related to its efficacy. Methods: We searched the PubMed and China National Knowledge Infrastructure (CNKI) databases for relevant Chinese-language and English-language literature published from January 1988 to October 2022. The literature was screened manually at three levels: title, abstract, and full text, to identify articles related to CHM and their mechanism of regulating tumor immunity. Key Content and Findings: By further classifying the CIC, it was confirmed that CHM can regulate the activation of dendritic cells (DCs) and macrophages and promote the presentation of tumor antigens. Meanwhile, CHM can also reverse tumor-immune escape by enhancing T-cell proliferation and infiltration. In addition, CHM can also enhance the antitumor ability of the body by regulating the killing process of tumor cells. Conclusions: The theory of a CIC is of guiding significance to regulating tumor immunity via CHM.

Production of iron-enriched yeast and it's application in the treatment of iron-deficiency anemia.

Iron deficiency anemia (IDA) is one of the most serious forms of malnutrition. Wild type strains of Saccharomyces cerevisiae have higher tolerance to inorganic iron and higher iron conversion and accumulation capacity. The aim of this study was to investigate the effect of S. cerevisiae enriched iron as a potential organic iron supplement on mice with iron deficiency anemia. 60 male Kunming mice (KM mice, with strong adaptability and high reproduction rate, it can be widely used in pharmacology, toxicology, microbiology and other research) were randomly divided into normal control group and iron deficiency diet model group to establish IDA model. After the model was established, IDA mice were randomly divided into 5 groups: normal control group, IDA group, organic iron group (ferrous glycinate), inorganic iron group (ferrous sulfate) and S. cerevisiae enriched iron group. Mice in the experimental group were given different kinds of iron by intragastric administration once a day for 4w. The results showed that S. cerevisiae enriched iron had an effective recovery function, and the body weight and hematological parameters of IDA mice returned to normal levels. The activities of superoxide dismutase, glutathione peroxidase and total antioxidant capacity in serum were increased. In addition, the strain no. F8, able to grow in an iron-rich environment, was more effective in alleviating IDA and improving organ indices with fewer side effects compared to ferrous glycinate and ferrous sulfate groups. This study suggests that the iron-rich strain no. F8 may play an important role in improving IDA mice and may be developed as a new iron supplement.

Discrimination and prediction of Qingzhuan tea storage year using quantitative chemical profile combined with multivariate analysis: Advantages of MRMHR based targeted quantification metabolomics.

The duration of storage significantly influences the quality and market value of Qingzhuan tea (QZT). Herein, a high-resolution multiple reaction monitoring (MRMHR) quantitative method for markers of QZT storage year was developed. Quantitative data alongside multivariate analysis were employed to discriminate and predict the storage year of QZT. Furthermore, the content of the main biochemical ingredients, catechins and alkaloids, and free amino acids (FAA) were assessed for this purpose. The results show that targeted marker-based models exhibited superior discrimination and prediction performance among four datasets. The R2Xcum, R2Ycum and Q2cum of orthogonal projection to latent structure-discriminant analysis discrimination model were close to 1. The correlation coefficient (R2) and the root mean square error of prediction of the QZT storage year prediction model were 0.9906 and 0.63, respectively. This study provides valuable insights into tea storage quality and highlights the potential application of targeted markers in food quality evaluation.

Quercetin Limits Tumor Immune Escape through PDK1/CD47 Axis in Melanoma.

Quercetin (3,3[Formula: see text],4[Formula: see text],5,7-pentahydroxyflavone) is a bioactive plant-derived flavonoid, abundant in fruits and vegetables, that can effectively inhibit the growth of many types of tumors without toxicity. Nevertheless, the effect of quercetin on melanoma immunology has yet to be determined. This study aimed to investigate the role and mechanism of the antitumor immunity action of quercetin in melanoma through both in vivo and in vitro methods. Our research revealed that quercetin has the ability to boost antitumor immunity by modulating the tumor immune microenvironment through increasing the percentages of M1 macrophages, CD8[Formula: see text] T lymphocytes, and CD4[Formula: see text] T lymphocytes and promoting the secretion of IL-2 and IFN-[Formula: see text] from CD8[Formula: see text] T cells, consequently suppressing the growth of melanoma. Furthermore, we revealed that quercetin can inhibit cell proliferation and migration of B16 cells in a dose-dependent manner. In addition, down-regulating PDK1 can inhibit the mRNA and protein expression levels of CD47. In the rescue experiment, we overexpressed PDK1 and found that the protein and mRNA expression levels of CD47 increased correspondingly, while the addition of quercetin reversed this effect. Moreover, quercetin could stimulate the proliferation and enhance the function of CD8[Formula: see text] T cells. Therefore, our results identified a novel mechanism through which CD47 is regulated by quercetin to promote phagocytosis, and elucidated the regulation of quercetin on macrophages and CD8[Formula: see text] T cells in the tumor immune microenvironment. The use of quercetin as a therapeutic drug holds potential benefits for immunotherapy, enhancing the efficacy of existing treatments for melanoma.

Ethyl-acetate extract of Spatholobi Caulis blocked the pro-metastatic support from the hemato-microenvironment of colon cancer by specific disruption of tumor-platelet adhesion.

BACKGROUND: Within the pro-metastatic hemato-microenvironment, interaction between platelets and tumor cells provides essential support for tumor cells by inducing Epithelial-Mesenchymal Transition (EMT), which greatly increases the stemness of colon cancer cells. Pharmacologically, although platelet deactivation has proved to be benefit against metastasis, its wide application is severely restricted due to the bleeding risk. Spatholobi Caulis, a traditional Chinese herb with circulatory promotion and blood stasis removal activity, has been proved to be clinically effective in malignant medication, leaving its mechanistic relevance to tumor-platelet interaction largely unknown. METHODS: Firstly, MC38-Luc cells were injected into tail-vein in C57BL/6 mice to establish hematogenous metastasis model and the anti-metastasis effects of SEA were evaluated by using a small-animal imaging system. Then, we evaluated the anti-tumor-platelet interaction efficacy of SEA using a tumor-specific induced platelet aggregation model. Platelet aggregation was specifically induced by tumor cells in vitro. Furthermore, to clarify the anti-metastatic effects of SEA is mainly attributed to its blockage on tumor-platelet interaction, after co-culture with tumor cells and platelets (with or without SEA), MC38-Luc cells were injected into the tail-vein and finally count the total of photons quantitatively. Besides, to clarify the blocking pattern of SEA within the tumor-platelet complex, the dependence of SEA on different fractions from activated platelets was tested. Lastly, molecular docking screening were performed to screen potential effective compounds and we used ß-catenin blockers to verify the pathways involved in SEA blocking tumor-platelet interaction. RESULTS: Our study showed that SEA was effective in blocking tumor-platelet specific interaction: (1) Through CCK-8 and LDH assays, SEA showed no cytotoxic effects on tumor cells and platelets. On this basis, by the tail vein injection model, the photon counts in the SEA group was significantly lower than model group, indicating that SEA effectively reduced metastasis. (2) In the "tumor-platelet" co-culture model, SEA effectively inhibited the progression of EMT and cancer stemness signatures of MC38 cells in the model group. (3) In mechanism study, by using the specific inhibitors for galectin-3 (GB1107) andWNT (IWR) respectively, we proved that SEA inhibits the activation of the galectin-3-mediated ß-catenin activation. CONCLUSION: By highlighting the pro-metastatic effects of galectin-3-mediated tumor-platelet adhesion, our study provided indicative evidence for Spatholobi Caulis as the representative candidate for anti-metastatic therapy.

Identification of sedative-hypnotic compounds shared by five medicinal Polyporales mushrooms using UPLC-Q-TOF-MS/MS-based untargeted metabolomics.

BACKGROUND: Five Polyporales mushrooms, namely Amauroderma rugosum, Ganoderma lucidum, G. resinaceum, G. sinense and Trametes versicolor, are commonly used in China for managing insomnia. However, their active components for this application are not fully understood, restricting their universal recognition. PURPOSE: In this study, we aimed to identify sedative-hypnotic compounds shared by these five Polyporales mushrooms. STUDY DESIGN AND METHODS: A UPLC-Q-TOF-MS/MS-based untargeted metabolomics, including OPLS-DA (orthogonal projection of potential structure discriminant analysis) and OPLS (orthogonal projections to latent structures) analysis together with mouse assays, were used to identify the main sedative-hypnotic compounds shared by the five Polyporales mushrooms. A pentobarbital sodium-induced sleeping model was used to investigate the sedative-hypnotic effects of the five mushrooms and their sedative-hypnotic compounds. RESULTS: Ninety-two shared compounds in the five mushrooms were identified. Mouse assays showed that these mushrooms exerted sedative-hypnotic effects, with different potencies. Six triterpenes [four ganoderic acids (B, C1, F and H) and two ganoderenic acids (A and D)] were found to be the main sedative-hypnotic compounds shared by the five mushrooms. CONCLUSION: We for the first time found that these six triterpenes contribute to the sedative-hypnotic ability of the five mushrooms. Our novel findings provide pharmacological and chemical justifications for the use of the five medicinal mushrooms in managing insomnia.

Pterostilbene suppresses gastric cancer proliferation and metastasis by inhibiting oncogenic JAK2/STAT3 signaling: In vitro and in vivo therapeutic intervention.

BACKGROUND: Gastric cancer (GC) represents a significant health burden with dire prognostic implications upon metastasis and recurrence. Pterostilbene (PTE) has been proven to have a strong ability to inhibit proliferation and metastasis in other cancers, while whether PTE exhibits anti-GC activity and its potential mechanism remain unclear. PURPOSE: To explore the efficacy and potential mechanism of PTE in treating GC. METHODS: We employed a comprehensive set of assays, including CCK-8, EdU staining, colony formation, flow cytometry, cell migration, and invasion assays, to detect the effect of PTE on the biological function of GC cells in vitro. The xenograft tumor model was established to evaluate the in vivo anti-GC activity of PTE. Network pharmacology was employed to predict PTE's potential targets and pathways within GC. Subsequently, Western blotting, immunofluorescence, and immunohistochemistry were utilized to analyze protein levels related to the cell cycle, EMT, and the JAK2/STAT3 pathway. RESULTS: Our study demonstrated strong inhibitory effects of PTE on GC cells both in vitro and in vivo. In vitro, PTE significantly induced cell cycle arrest at G0/G1 and S phases and suppressed proliferation, migration, and invasion of GC cells. In vivo, PTE led to a dose-dependent reduction in tumor volume and weight. Importantly, PTE exhibited notable safety, leaving mouse weight, liver function, and kidney function unaffected. The involvement of the JAK2/STAT3 pathway in PTE's anti-GC effect was predicted utilizing network pharmacology. PTE suppressed JAK2 kinase activity by binding to the JH1 kinase structural domain and inhibited the downstream STAT3 signaling pathway. Western blotting confirmed PTE's inhibition of the JAK2/STAT3 pathway and EMT-associated protein levels. The anti-GC effect was partially reversed upon STAT3 activation, validating the pivotal role of the JAK2/STAT3 signaling pathway in PTE's activity. CONCLUSION: Our investigation validates the potent inhibitory effects of PTE on the proliferation and metastasis of GC cells. Importantly, we present novel evidence implicating the JAK2/STAT3 pathway as the key mechanism through which PTE exerts its anti-GC activity. These findings not only establish the basis for considering PTE as a promising lead compound for GC therapeutics but also contribute significantly to our comprehension of the intricate molecular mechanisms underlying its exceptional anti-cancer properties.

Diagnostic Potential of microRNA-122 for Stage Classification in Patients with HBV-Related Cirrhosis.

Objective: Previous studies have suggested that microRNA-122 has a relatively high diagnostic value for chronic viral hepatitis detection. In this study, we evaluated the diagnostic value of serum microRNA-122 in different stages of HBV-related cirrhosis，and serum microRNA-122 may serve as a potential biomarker for staging HBV related cirrhosis patients.. Methods: A total of 80 patients with HBV-related cirrhosis were included. Patients were characterized according to Child-Pugh score, laboratory parameters, and complications, and divided into compensated cirrhosis group and decompensated cirrhosis group. Wherein, the compensatory group for liver cirrhosis includes 21 patients, the compensatory group has 59 patients. Blood was collected from all patients, and RT-qPCR analyzed the expression levels of microRNA-122. Results: Serum microRNA-122 was decreased, while Child-Pugh score, Meld score, Prothrombin time, total bilirubin, and Direct bilirubin were higher in a decompensated group compared to the compensated group (all P < .05). For further stage classification, the mean serum microRNA-122 level was higher in stage 1 (11.3±5.1, compensated cirrhosis) compared to stage 2~5 (8.5±4.2, 4.9±1.0, 4.7±1.6, 3.5±1.1, decompensated cirrhosis, all P < .05). The expression of serum microRNA-122 independent of Child-Pugh score and complications, including ascites, varices, HCC (P > .05).However it was affected by Meld score and Prothrombin time (P < .05). Moreover, ROC analysis indicated microRNA-122 could differentiate compensated HBV-related cirrhosis (0.97 of AUC, P < .01). Furthermore, it could differentiate patients in stage 1 (compensated cirrhosis without esophageal varices) from HBV-related cirrhosis (0.91 of AUC, P < .01), with a sensitivity of 77.8% and satisfactory specificity of 88.7%. The significance of the relationship between the decrease in serum microRNA-122 levels and the stage of liver cirrhosis will be beneficial. Conclusion: Our results strongly support the diagnostic value of serum microRNA-122 as a potential biomarker of stage classification in patients with HBV-related cirrhosis, which could facilitate risk stratification and careful management. Provide new biomarkers for the diagnosis of patients with hepatitis B cirrhosis.

The effects of different types of Tai Chi exercises on preventing falls in older adults: a systematic review and network meta-analysis.

OBJECTIVES: Few studies comparing the effects of different types of Tai Chi exercises on preventing falls in older adults. We compared the effects for finding an optimal intervention. METHODS: We searched 12 databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and so on, from their inception to January 13, 2023. Randomized controlled trials incorporating different types of Tai Chi for preventing falls in older adults were included. The outcome measures were the incidence of falls and Berg Balance Scale (BBS). Network meta-analysis (NMA) was conducted using Stata 15.1 based on a frequentist framework. RESULTS: Seventeen trials were eligible, including 3470 participants and four types of Tai Chi. They were 24-form simplified Tai Chi (24-form), Yang style Tai Chi (Yang style), Sun style Tai Chi (Sun style) and Tai Chi exercise program (TCEP). In paired meta-analysis, for incidence of falls, 24-form (Relative Risk (RR) = 0.59, 95% confidence interval (CI) [0.40, 0.86]) was more efficient than the control group. For BBS outcome, 24-form (MD (mean difference) = 2.32, 95% CI [1.42, 3.22]) was better than the control group. In the NMA, the results of incidence of falls were as follows: 24-form > Yang style > Sun style > control > TCEP. The rank probability of BBS was as follows: 24-form > TCEP > Yang style > control. CONCLUSION: Among the four types of Tai Chi studied, the 24-form simplified Tai Chi has shown better efficacy than other types.

Visualizing research trends and identifying hotspots of herbal components for treating cardiovascular diseases: A bibliometric analysis from 2000 to 2023.

OBJECTIVE: The objective of this study was to investigate the global research trends in herbal medicine for the treatment of cardiovascular disease (CVD) from 2000 to 2023. A bibliometric approach was employed to analyze international collaborations, knowledge structures, emerging trends, and research frontiers. METHOD: The Web of Science (WOS) core collection was utilized as the database, employing the search formula (((TS = (traditional Chinese medicine)) OR TS = (Chinese herbal medicinal ingredient)) OR TS = (Chinese herbal medicinal constituent)) AND TS = (cardiovascular disease) to conduct the search. The search period spanned from January 1, 2000, to February 14, 2023, and the literature type included articles and reviews. RESULTS: A total of 1478 papers were included in the analysis after searching the WOS database and excluding conference proceedings, news articles, retractions, editorials, and letters. China demonstrated the highest number of publications, followed by the United States and Taiwan (China). The institution with the highest publications was the Chinese Academy of Medical Sciences. China, the United States, and India were the main countries involved in research in this field, and there was significant collaboration among them. The hotspots related to herbal components for treating cardiovascular diseases from 2000 to 2023 included systematic reviews, ischemic reperfusion injury, global burden, type 2 diabetes, and protection. CONCLUSION: This paper provides a reference for the future development of herbal research in cardiovascular aspects by revealing the current status, hotspots, and trends of global herbal research in cardiovascular factors over more than 20 years. Identification of potential collaborators and institutions can assist researchers in exploring new directions for future research and discovering new perspectives for potential collaborations in this field.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.